We will examine the pulmonary hemodynamic responses to various pulmonary and systemic stiumli and how these responses are modified by superimposition of one upon the other. The pulmonary stimuli include pulmonary embolism and changes in alveolar gas compostition and transpulmonary pressures. Systemic stiumli include systemic hypotension, changes in cerebrospinal fluid composition, and others which have been associated with the development of pulmonary insufficiency to which pulmonary vasomotor responses may contribute. The experiments will be carried out using isolated cat lungs and dog lung lobes perfused in situ. In these preparations, nervous, hormonal and local vasomotor influences and mechanical influences can be examined separately or in concert, all wing identification of the mechanisms involved. Hemodynamic responses will be identified using the low viscosity bolus technique for determining the longitudinal distribution of vascular resistance, and ether and dye dilution techniques for determining the distribution of vascular volumes and compliances. We will also examine the influence of lung uptake and inactivation of pulmonary vasoactive drugs on the pulmonary hemodynamic responses to these drugs. The hemodynamic responses to the drugs will be characterized as described above, and in addition we will measure the quantities of the drugs which are inactivated on passage through the lung. We will then correlate the changes in the hemodynamic responses with changes in the inactivation mechanisms.